Clinical chemical analyzers are known in the art which are capable of analyzing multiple analytes. These conventional chemical analyzers use ultraviolet/visible spectrophotometer and ion selective electrode technology to analyze typically from 20 to 32 chemicals, enzymes and ions from one fluid sample.
Several problems arise with the use of conventional clinical chemical analyzers. First, most assays are performed by indirect detection of the actual analyte by coupling an enzyme through a chemical reaction to yield a colored substance. The reagents involved tend to be unstable. Second, many of the test methods are non-linear in their response. Finally, the sample manipulation robotics technology involved is very complex.
The current clinical chemical analyzers also tend to be relatively slow in the production of results. A physician who orders one or more assays using these conventional systems optimally wants results back in 30 to 60 minutes, but usually has to wait 24 to 48 hours. In an effort to make the conventional clinical chemical analyzers to use by non-skilled technicians, manufacturers have tried to make all the required reagents in liquid form. This has resulted in even more complex chemistry and increased problems of stability.
Nuclear magnetic resonance (NMR) spectroscopy is a standard technique for identifying molecular structure and content. However, present NMR clinical spectrometers are ill suited for clinical chemistry applications.
One problem is the tremendous magnetic fringing fields created by conventional NMR instruments, which generally have magnetic field strengths in the range of 9 to 12 Tesla. These magnetic fields are of such a magnitude that ferromagnetic objects of any appreciable mass (0.1 ounce or more) would accelerate toward the NMR magnet while in operation, posing a condition capable of causing injury to personnel in the process. The very large magnetic field strengths generated by conventional analytic NMR magnets are obtained by the use of superconductive coils immersed in coolant baths using cryogens (liquid helium and nitrogen) to reduce the temperature of the coils to a few degrees Kelvin above absolute zero. The large magnetic fields generated by the superconductive coils will, if unshielded, also cause disturbances in nearby electronic apparatus, and have the possible capability of erasing nearby magnetic media (computer tapes, disks).
For this reason, conventional NMR spectrometers are sited within their own rooms suited for the purpose. Ferromagnetic shielding, such as iron or steel plates, are erected remotely, either around the walls of the room or as a portion of the structure of the building in order to increase uniformity of the generated NMR magnetic field, decrease disturbance with surrounding electronic- and magnetic-based devices, contain the fringing field and avoid large forces that might result between the shielding and the magnet itself. Conventional NMR shielding requirements make NMR spectroscopy unsuitable for siting on a vehicle or within relatively restricted areas.
Another problem with conventional NMR spectroscopy is the time that is involved in performing an assay. The NMR magnet has an axial bore in which there is located a prolate spheroidal area of maximum magnetic field uniformity, the so-called "sweet spot." A sample tube is manually filled to a predetermined level with the solution to be assayed and is placed within this "sweet spot" in the axial bore. A signal/sensor radio frequency coil producing an oscillating magnetic field orthogonal to the static field of the magnet surrounds this sample holding tube. Because of variations in the physical placement of the sample and the fluid analyte level, it is necessary to electronically adjust the magnet homogeneity of, or shim, each sample individually. To provide for an increase in uniformity of the field, the sample is spun about the main coil's axis. This sample must therefore be contained in a totally separate container, which container must be placed inside the magnet for each sample to be tested and later removed. For these and other reasons, conventional NMR spectrometers require a large amount of time and expertise to operate. If these problems with NMR spectroscopy could be solved, nuclear magnetic resonance could form the basis for a clinical chemistry analyzer.